You Will Get Prostate Cancer

Editors Note: The following article is the second installment of "Death Threats," a 3-part series on the three greatest health risks facing men. These stories give a personal look into what men and their families go through when diagnosed with these diseases. The other two Death Threats parts feature stroke and heart disease.

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"He's in the hospital."

"The cancer has spread."

"We're hoping for the best."

It's amazing, the life-changing capacity of a single phone call. Just a minute before, my wife and I were happily packing for a vacation, our tangle of clothes in the middle of the room, the price tag still attached to her new Lycra swimsuit. Then came the call from Ellen's mom. Her dad's prostate cancer was back, and it had spread to his spine. We hastily changed our travel plans. Destination: Los Angeles.

A dashing, fit, silver-haired professor of psychology at UCLA, Michael Goldstein had had a brush with prostate cancer 3 years earlier. Although he hadn't suffered the symptoms that sometimes emerge—an unrelenting urge to urinate, a burning sensation when he did—a blood test at his annual physical indicated high levels of prostate-specific antigen, or PSA. His family had been surprised, given the trademark high energy that allowed him to teach graduate seminars, conduct his own research, and fly to and from Europe several times a year to lecture in Rome, London, and Amsterdam. After he opted to have the cancerous gland removed, his doctors pronounced him cured, and he threw himself back, with gusto, into his work, his family, his life.

We arrived in Los Angeles the morning after the phone call and drove straight to the hospital. When we walked into my father-in-law's room, he seemed tired, a trifle sallow, but otherwise still his optimistic, glass-half-full self. A nurse was teaching him to walk with a back brace that looked about as comfortable as a corset. Outside, a dry wind rattled the eucalyptus fronds, but here the air smelled of disinfectants, and the light was eternal fluorescent.

I'd last seen him at our wedding, 6 months earlier, on a snowy, breezy afternoon in Manhattan. Ellen walked down the aisle on her father's arm as he radiated paternal pride. At the reception, he charmed the guests with a toast only a father could give: "As a girl, Ellen loved to hear stories—and I always knew she'd marry a man who would regale her with story after story...."

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Now, as we tried to summon comforting, cliche-free words, he teetered down the corridor, tracing his right hand along the rail for support. I helped him practice his new steps, his arm slung across my shoulder. A week later, tests confirmed that the cancer had, in fact, spread. Somehow he maintained his confident, cheerful façade, yet the creases around his eyes hinted that he knew. He was, after all, a man of science. The little lifts of good news—We've confined the cancer to just a few spots on the spinal column, some mild radiation will take care of it, the worst thing will be the damned brace—were only temporary lulls in a gathering storm.

In less than 7 months, he was gone.

About 635 men a day are diagnosed with prostate cancer.

It's a frightening figure. But perhaps not scary enough, since many young men still dismiss the disease as just another unavoidable side effect of aging.

Here's why you should take it more seriously: Groundbreaking autopsy studies from Wayne State University show that prostate-cancer risk rises 10 percentage points with each passing decade. Thirty-year-olds have a 30 percent chance of carrying a trace of the cancer, fortysomethings a 40 percent chance, and so on. Sure, it usually progresses so slowly that most men die of something else first, but prostate cancer does kill more than 30,000 men annually—1 percent are under the age of 55, and 8 percent are under age 65. More virulent forms, like my father-in-law's, can kill in less than a year.

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The prostate gland, scarcely larger than a cherry tomato, is tucked between the bladder and the urethra, ideally situated to perform its primary function: to secrete seminal fluid for ejaculation, so that sperm can be propelled through the urethra and out to begin their mad dash to meet a lonely ovum. It's ironic, then, that a gland that plays such a central role in creating life—greasing the skids, as it were—threatens to end a man's life as well.

The most important men in my life have been dancing around this killer for a few years now. Not only did the disease take my father-in-law at the age of 67, but my own 76-year-old father is at increased risk. His most recent blood test revealed a moderately elevated PSA. My grandfather also developed prostate cancer as he struggled with his final, fatal pneumonia. (He was 92 at the time, so a urologist might say he "lived long enough" to contract the illness.) And, of course, I have the number-one risk factor: I'm a man.

My brother-in-law, Peter, knows the danger well, the disease having cut short the lives of two men in his family. Recently, he confided his anxiety: "Dude, I'm toast."

So, on a warm June morning, I visit Daniel Petrylak, M.D., an oncologist at Columbia Presbyterian Hospital's Irving Cancer Center, in New York City. Dr. Petrylak, a leading prostate-cancer researcher, has helped shape the course of treatment. With me is a list of questions you'd expect a journalist writing a story about prostate cancer to be carrying. But I also carry a second list, one that probably reads a lot like yours:

1. Exactly how at risk am I?2. Should I have a PSA test?3. What can I do to reduce my risk?

And then I have a final, more personal question: Could my father-in-law have been saved?

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"So you're concerned that you're at risk?" asks Dr. Petrylak, a handsome, dapper man with deep brown eyes. His gaze flits back and forth from me to his computer screen.

"It's been on my mind," I respond.

"How old are you?"

"Just turned 40."

"All men over 50 should have a PSA test," says Dr. Petrylak. "But the earlier a man and his doctor can catch prostate cancer, the broader the range of treatment options."

PSA, a protein manufactured in the prostate, is measured with a simple blood test. Men with prostate cancer, or even enlargement of the prostate, have higher levels of PSA, because it rises in response to any type of trauma. Dr. Petrylak explains that a PSA count above 4.0 (as measured in nanograms per milliliter) raises a red flag, although a recent study suggests that a bigger threat is a PSA that rises quickly.

If the PSA score looks alarmingly elevated, the urologist will usually suggest a biopsy of the gland. Likewise if he detects a suspicious lesion during a digital rectal exam. After the biopsy, the tissue is then analyzed under a microscope. If it's found to be cancerous, the clinicians assign a Gleason score, which ranges from 2 to 10 and indicates the kind of cancer that's present and whether it could aggressively spread to other parts of the body. This grading system, developed by pathologist Donald Gleason, M.D., in 1977, is used with a system of stages (from 1 to 4) to steer a man to a preferred form of treatment. Depending on the cancer's severity, a patient can choose from various options, such as a radical prostatectomy (surgical removal of the gland), radiation therapy (nuking the cancer), surgical castration (removal of the testicles to halt the production of testosterone, which can fuel the cancer), hormone therapy (sometimes called "chemical castration"), or a combination of these treatments.

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When confronted with a PSA count of 7.0, my father-in-law opted for a prostatectomy. Soon after, his PSA level dropped back to near zero, and his doctor declared that the disease had been beaten. For weeks, my father-in-law joked that he'd avoided the ultimate male fear, "the snip-snip." He pushed ahead with his active life, traveling from Los Angeles to New York City to see Ellen and me, and then on to Europe, where he lectured on schizophrenia and bipolar dis-orde—rand found a way to fly in and out of Brussels, where his son lived, in order to dandle his new granddaughter on his knee.

What he didn't know was that his prostate cancer wasn't beaten. It was hiding.

"We now think of cancer as a genetic disease."

That's William Isaacs, M.D., a leading prostate-cancer researcher at Johns Hopkins University. According to Dr. Isaacs, 91 percent of all prostate cancers are sparked by DNA that becomes corroded over the course of a man's life (more on that in a moment). The other 9 percent are also triggered by a hiccup in the helix, except that this flaw is passed down from generation to generation. In fact, if a man younger than 55 develops prostate cancer, there's a good chance that he has his dad to thank—more than 40 percent of those cases, researchers now believe, involve one of several mutant genes passed from fathers to sons.

Here's another way to look at Dr. Isaacs's breakdown: Nine in 10 men who develop prostate cancer were actually born with healthy genetic blueprints for their prostates. In these men, DNA damage results from what Dr. Isaacs calls "somatic changes triggered by environmental issues." In other words, diet, smoking, lack of exercise—all the gremlins this magazine continually warns you about.

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Another of these "environmental issues," and potentially the most powerful of all, is infection. "Our natural immunities kill bacteria effectively—without them, we couldn't live," explains Dr. Isaacs. "But our immune responses are also potent in altering our own DNA over a lifetime. Call it ‘collateral damage.' " So, in an effort to completely wipe out one enemy, our bodies may inadvertently set the stage for another, more powerful opponent to rise from the glandular rubble.

The emerging hypothesis—researchers shy away from the word "consensus"—is that the presence and virulence of prostate cancer are intertwined with inflammation, the cellular signpost that indicates an immune reaction. And, oddly, the best tool for measuring prostate inflammation may be a heart test.

For several years now, smart cardiologists have been assessing their patients' blood levels of C-reactive protein (CRP), one of the body's main inflammation markers. High levels—over 3 milligrams per liter—are generally considered to be a risk factor for a heart attack, since inflammation can signal the presence of arterial plaque. So doctors at Mount Sinai Medical Center in New York City theorized that if elevated CRP levels could predict heart trouble, then they might also help forecast prostate cancer. The docs were right: After analyzing the bloodwork of 114 men with prostate cancer, the researchers discovered that the men's CRP and PSA scores rose and fell in unison.

More research is needed to confirm this connection, but the implications are significant. Not only might CRP testing be used as a tool for diagnosing prostate cancer, but it could also serve as an early-warning system that helps men avoid the disease.

Just as intriguing, says Dr. Isaacs, is how an out-of-whack immune response may figure into the inherited form of the disease. He had been studying families rife with prostate cancer for years when, in 2002, he and his colleagues made a discovery on chromosome 1. Through their analysis of about 200 families, they identified RNASEL, a gene that encodes an enzyme whose job it is to prevent viral infection. A mutation in the gene basically opens up a "pathway" to prostate inflammation.

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Still, Dr. Isaacs believes that, unlike with BRCA1, the gene whose mutated form almost always accurately predicts breast cancer, there's no one genetic flaw that causes prostate cancer. "Prostate cancer may be more complex than breast cancer," he says. "We know that many genes are affected."

I wonder aloud whether RNASEL or some other obscure genetic culprit caused my father-in-law's death—after all, his own father suffered from the disease for years before succumbing in the '80s. When I mention my father-in-law's case, Dr. Isaacs perks up. Apparently, even when you take DNA into account, it's uncommon for a healthy, active man in his mid-60s to fall under the scythe of the disease in a matter of months. "Guys like your father-in-law . . . these guys fascinate us," he says. "Clinically speaking, we really can't explain them. The example I always use is Frank Zappa, who was diagnosed at 52 and went quickly."

I smile grimly to myself as Dr. Isaacs links these rare cases. He's conjured a couple of fond adolescent memories: the famous Zappa album cover Ship Arriving Too Late to Save a Drowning Witch; the annoyingly catchy lyrics of "Valley Girl" blaring ubiquitously from Trans Am stereos in the summer of 1982; barf out; gag me with a spoon. Frank Zappa had lived in the Hollywood Hills, where on warm afternoons his children, Moon Unit and Dweezil, tagged along with other neighborhood kids, roaming the box canyons high above a blanket of smog. I now wonder if they remember one of their playmates, a slender, angular girl with parted Marcia Brady hair and a quick, sarcastic wit.

The girl who'd one day become my wife.

For a man weaned on hush puppies and barbecue, I've struggled with being married to a strict vegetarian, grumbling at the menu restrictions she's cruelly imposed on me, such as steamed spinach and stir-fried tofu. In the long run, though, I may have her to thank for a healthy, cancer-free life.

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A colleague of Dr. Isaacs, Bill Nelson, M.D., has researched the role of diet in prostate cancer and offers a few rules to, in the fullest sense of the word, live by. First, given that the common denominator for the disease seems to be inflammation and the body's auto-immune responses, he pounds the pulpit for foods whose chemistry can combat infection: fruits and vegetables—the "broccoli as cure for cancer" idea in vogue for the past decade. Noting that Southeast Asian men have much lower rates of prostate cancer—and that their first- and second-generation immigrant sons in Western countries have rates comparable to those of native-born Caucasians—he also preaches the Gospel of Soy.

"And think about taking supplements, like selenium and vitamin E, as well as such anti-inflammatory medications as aspirin and ibuprofen," he says. And, for God's sake, he notes, please avoid charbroiled meat; carcinogens in it have been shown to disproportionately cause prostate cancer in lab studies.

Another way to reduce the risk is to engage the prostate's self-cleaning cycle. Researchers in Australia recently queried more than 1,000 men with prostate cancer about their ejaculation rates and compared the results with data obtained from a comparable group of healthy men. These researchers discovered that men who ejaculated frequently between the ages of 20 and 50 were at markedly lower risk of developing prostate cancer. Even more provocatively, men in their 20s who ejaculated at least five times a week were one-third less likely to develop aggressive prostate cancer during their mature years. All those high-school P.E.-class jokes assume new meaning when I ponder the clear health benefits of chronic masturbation.

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Conclusion: Prostate cancer can often be prevented through the basics of a healthy diet and vigorous exercise, whether one plays on an intramural basketball team or in the privacy of the bathroom with the skilled assistance of the December Playmate of the Month.

And if prevention fails? Detection can succeed in saving us.

"The incidence in younger men is soaring," observes Dr. Isaacs, "but only because detection methods have improved exponentially." However, he adds, this also raises new questions. "How do we use screening effectively? Are we overdiagnosing and overtreating, especially in younger patients? There are so many controversial areas of prostate cancer."

Like other clinicians, Dr. Petrylak feels the PSA test has its limits in predicting the presence of cancer: "We need better, more specific tests at this point." He frequently consults with David Bostwick, whose epony-mous Bostwick Laboratories has identified a new marker in urine and has brought the first non-PSA test onto the market.

Created in the Netherlands by Jack Schalken, M.D., the uPM3 test—"the first real prostate test to come out of the genomics revolution"—requires massaging of the prostate gland through a digital rectal examination. This dislodges cells and bits of tissue, which are then flushed out into the urine. The patient immediately heads off to the bathroom to pee into a special cup, where the expressed cells and tissues are collected. The urine specimen is then ferried to a lab, where clinicians must analyze the cell's RNA within 72 hours—a more complicated and time-consuming process than looking at PSA, but also more likely to yield an accurate diagnosis.

The test's specificity—its ability to identify the presence of cancer in a patient—has proved to be about 80 percent accurate; and its sensitivity, the ability to prove the absence of cancer, is likewise in the 80 percent range. The sensitivity of the PSA test also hovers in the 80 percent range, but its specificity never rises above 70 percent.

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Dr. Bostwick says it's an exciting time for early detection. By early 2006, the next generation of the uPM3 test—called the PCA3—will debut on the market from numerous labs all over the world and will yield, he says, close to 100 percent accuracy. It may render the standard PSA test obsolete.

But that's tomorrow. In my father-in-law's case, the usual tools for detecting prostate cancer failed to uncover his disease. And then, despite the arsenal of weapons available, his urologist was unable to eradicate every last malignant cell. As I discovered, one cell is all it takes.

In a weird twist, the only treatment that might have offered my father-in-law any hope of survival was the same one that's currently saving women by the score: the breast-cancer drug Taxotere. Lab studies in the late 1990s showed that the medication was surprisingly effective at combating late-term prostate cancer, prompting Dr. Petrylak to conduct his own trial. Last year, he published his results in the New England Journal of Medicine, in which he described the clear benefits of a chemotherapy regimen based on Taxotere. After cranking his data through various algorithms, he calculated a 20 percent spike in the survival rate among patients. Just as significant, he detailed dramatic improvements in quality of life, despite such debilitating side effects as osteoporosis and loss of sexual function. Dr. Petrylak acknowledges feeling a bittersweet pang when he hears a common refrain from his patients: "Doc, I feel like someone has taken the wind out of my sails."

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He's now concentrating on enhancing the benefits of Taxotere with a second drug. In a new blind trial, he'll develop a regimen for late-term prostate-cancer patients, combining Taxotere with Revlimid; the latter is akin to thalidomide, the drug originally used in pregnant women in the late 1950s to temper morning sickness but discontinued when many of the babies born to those women had birth defects. Dr. Petrylak hopes that, taken in tandem, Taxotere and Revlimid will reduce the cancer's toxicity and increase the efficacy of the treatment program. He expects the trial to grow to as many as 36 patients.

As much as I want Dr. Petrylak's trial to be a success, what I want even more is to avoid becoming one of its participants. When I mention this to him, he concurs with Dr. Nelson's recommendation: "A heart-healthy diet is a prostate-healthy diet." More important, a man should undergo an annual prostate examination, with semiannual PSA tests, beginning at age 40 if there's a strong family history of prostate cancer.

Last fall—calmly, uneventfully, with no abrupt outbreak of gray hair around the temples, no crow's feet around the eyes—I passed the milestone of my 40th birthday. One evening some weeks later, my wife and I sat down on the couch after dinner, and while she watched over my shoulder, I jotted down a list on a notepad: blood pressure, cholesterol, colonoscopy, prostate exam. The following afternoon, I was heading into Manhattan for my yearly physical, and I'd made a solemn promise to my wife.

Ellen pushed a wing of hair out of her eyes. "You make sure you check in with Dr. Beautyman about everything."

"I will."

She rapped me on the shoulder. "That means a prostate exam, too."

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"Dr. B. will probably refer me to a urologist." I knew that might take a while: the referral back-and-forth, the scheduling of an appointment, the rescheduling of the appointment because one of our newborn twin sons is sick. I had only a vague notion what the exam would entail but was content to put it off ad infinitum. With any luck, I could draw this out until my 41st birthday.

As I sat on the examination table the next afternoon, stripped to my skivvies under the paper gown, my strategy was firm. Dr. Beautyman strode into the room, a tall, fashionable woman in her 50s, a silk skirt and Manolo Blahniks showing from beneath her lab coat. We exchanged small talk as she snaked her stethoscope across my chest and back, listening to my heart and lungs. The kids are all doing well, no real problems this year, weight 155 pounds, blood pressure up a smidgen but normal for a 40-year-old man. She asked me to stand and slip my boxer shorts to the floor, turn my head, and cough while she checked my testicles for a hernia.

As I tugged the shorts back up, relieved that I'd gotten past that awkward moment, I broached the subject. "Now that I'm 40, Dr. Beautyman, do you recommend yearly prostate exams?"

A frown creased her face. "Did your father have prostate cancer?"

"No, but he has had an elevated PSA count. My father-in-law actually died of it, an unusually virulent case."

"I see," she said. She tapped her toe on the linoleum floor while making notes on my chart. I began to peel away the gown and reach toward the examination-room door, where my jeans, shirt, and peacoat hung from a hook.

"Don't get dressed yet," she said. She swiveled on her stool, stood, and placed the chart on top of the credenza. "Hop back onto the table and pull down your shorts, face the wall, and bring your knees to your chest." She rummaged through the credenza's lower drawer.

"I'm sorry?"

"Up on the table," she said. I heard the thwack of a rubber glove.

I lay on my side with my face to the wall, slid my shorts down below my ankles, and with one arm hugged my knees to my chest. The wall was painted beige, that colorless color.

I felt her hand on my hip, steadying my rear end as she eased her fingers in and thrust forward, a doctor's skilled, practiced technique. The shock lifted me an inch off the table's vinyl surface. For an instant, I felt her squeeze deep inside me, palming the soft contours of a ball I'd scarcely been aware I had.

A sharp pang of pain, a star shooting past the edge of sight.

"No suspicious lumps anywhere. You're good to go until next year."

She withdrew and I looked back quickly, saw a bright stain as she stripped off the glove and tossed it into a garbage canister.

"You can get dressed now. I'll call you as soon as I get the bloodwork back," she said. "If there's anything abnormal, we can discuss it then."

Back home, I sat on the couch, a twin propped in the crook of each arm, their hands flailing about their faces in hunger. There was no residual soreness from the exam, no pain. And no cause for concern. I should be grateful.

But instead, I knew I'd only embarked on a voyage that would last the rest of my life, a quintessentially male experience, one shared by millions of men all over the world. I glanced down into the clear blue stares of my babies. Some day, I knew, they'd join me in the journey.

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